A re-evaluation of the use of glyceryl trinitrate to assess the degree of adrenergic beta receptor blockade

Abstract

Adrenergic beta receptor blocking drugs have become an established part of medical practice. They are used primarily in the management of hypertension, ischaemic heart disease and cardiac arrhythmias. Since beta blockade is to a large extent dose dependent, it is important to determine whether sufficient of the drug has been given to inhibit the effects of endogenously released catecholamines. The most common testemployed in clinical practice is to measure the heart rate response during dynamic exercise. Unfortunately, formal exercise testing is not a simple procedure.In 1979, Fitzgerald introduced a new test of the degree of adrenergic beta receptor blockade using Glyceryl Trinitrate. From his studies,Fitzgerald concluded that the positive chronotropic effects of Glyceryl Trinitrate administration were due solely to sympathetically mediated reflexes. This conclusion, however, has been questioned by Hansson, Kofi Ekue and Zweifler; all suggesting that vagal withdrawal may also contribute a part in this response. My studies have shown that both vagal withdrawal and sympathetic stimulation are involved in the heart rate response to sublingual Glyceryl Trinitrate administration. Also, as people age there appears to be a bigger fall in arterial blood pressure and relative blunting of the heart rate response, probably reflecting relative insensitivity of the adrenoceptors in the arterial tree and the heart, resulting in a failure of the sympathetic nervous system to compensate for the fall in pressure. The Glyceryl Trinitrate induced tachycardia compares favourably with the tachycardia induced by sub-maximal bicycle exercise. The Glyceryl Trinitrate test was found to be very sensitive in detecting low levels of beta blockade, and would, therefore, be very useful, clinically, in outpatient departments or general practice to assess the degree of adrenergic beta blockade.